Halogenated 2,5-pyrrolidinediones: synthesis, bacterial mutagenicity in Ames tester strain TA-100 and semi-empirical molecular orbital calculations

The chloroimide 3,3-dichloro-4-(dichloromethylene)-2,5-pyrrolidinedione, a tetrachloroitaconimide, is the principal mutagen produced by chlorination o f simulated poultry chiller water. It is the second most potent mutagenic d isinfection by-product of chlorination ever reported. Six of seven new synt hetic analogs of this compound are direct-acting mutagens in Ames tester st rain TA-100. Computed energies of the lowest unoccupied molecular orbital ( E-LUMO) and of the radical anion stability (DeltaH(f)(rad) - DeltaH(f)) fro m MNDO-PM3 for the chloroimides show a quantitative correlation with the Am es TA-100 bacterial mutagenicity values. The molar mutagenicities of these direct acting mutagenic imides having an exocyclic double bond fit the same linear correlation (InMm vs. E-LUMO; In M-m vs. DeltaH(f)(rad) - DeltaH(f) ) as the chlorinated 2(5H)-furanones, including the potent mutagen MX, 3-ch loro-4-(dichoro-methyl)-5-hydroxy-2(5H)-furanone, a by-product of water chl orination and paper bleaching with chlorine. Mutagenicity data for related haloimides having endocyclic double bonds are also given. For the same numb er of chlorine atoms, the imides with endocyclic double bonds have signific antly higher Ames mutagenicity compared to their structural analogs with ex ocyclic double bonds, but do not follow the same E-LUMO or DeltaH(f)(rad) - DeltaH(f) correlation as the exocyclic chloroimides and the chlorinated 2( 5H)-furanones. Published by Elsevier Science B.V.